[Study on chemical components of Hypericum himalaicum and mechanism of anti-inflammatory based on network pharmacology and molecular docking technology].

The chemical constituents of ethyl acetate from Hypericum himalaicum were isolated by silica gel column chromatography, gel column chromatography, and high-performance liquid chromatography. The structure of the isolated compounds was identified by modern spectral techniques(NMR, MS, IR, and UV), and the potential anti-inflammatory targets and action pathways were analyzed and predicted by network pharmacology and molecular docking methods.Ten compounds were isolated from H. himalaicum and identified as 5,9,11-trihydroxy-3,3-dimethyl-3H,8H-benzo[6,7][1,4]dioxepino[2,3-f]chromen-8-one(1), betulinic acid(2), demethyltorosaflavone C(3), kaempferol(4), quercetin(5), hyperwightin B(6), toxyloxanthone B(7), 1,7-dihydroxy-xanthone(8), emodin(9), and 1,7-dihydroxy-4-methoxy-xanthone(10). Among them, compound 1 was a new compound, and compounds 2-10 were isolated from H. himalaicum for the first time. Network pharmacology screened 60 key anti-inflammatory targets. By acting on TNF, AKT1, CASP3, and other key targets, involving PI3K-AKT signaling pathway, IL-17 signaling pathway, VEGF signaling pathway, MAPK signaling pathway, and other signaling pathways, and phosphorylation, cell migration and movement, protein tyrosine kinase, and other biological processes were regulated to achieve anti-inflammatory effects. The results of molecular docking show that the above components have good binding properties with the core targets.

[Polycyclic polyprenylated acylphloroglucinols from Hypericum species and their biological activities].

Hypericum species are distributed widely in China, especially in the southwest. This genus is rich in species types in China, including 55 species and 8 subspecies. The main chemical constituents of Hypericum species are flavonoids, xanthones and polycyclic polyprenylated acylphloroglucinols(PPAPs). PPAPs are characterized by polycyclic and branched-chain substitutions in their structures, which make their structure types diverse. Moreover, they have been found to have antitumor, antiviral, antibacterial, anti-inflammatory and other biological activities. This research classified and summarized 344 polycyclic polyprenylated acylphloroglucinols from Hypericum plants in order to provide a scientific basis for further development and utilization of PPAPs from the genus.

Essential Oil from Carpesium abrotanoides L. Induces Apoptosis via Activating Mitochondrial Pathway in Hepatocellular Carcinoma Cells.

The effects of essential oil from Carpesium abrotanoides L. (CAEO) on the proliferation and apoptosis of human hepatic cancer cells were investigated in this study. MTT assays indicated that CAEO inhibited the proliferation of HCC cells with the IC50 values ranging from 41.28±3.06 to 130.36±20.79 µg/mL. Moreover, many obviously nuclear morphological changes of apoptotic cells in CAEO-treated HepG2 cells were detected by Hoechst 33258 staining and fluorescence microscopy. Flow cytometry was used to detect cell apoptosis and cell cycle, and noticeable findings showed that CAEO arrested cell-cycle at S and G2/M phases. The decreased Bcl-2/Bax protein ratio and the activation of caspase-3, caspase-9 were also detected by Western blotting. All results suggested that CAEO is a potential agent to fight against liver cancer, and the mitochondria-mediated intrinsic apoptotic pathway could be involved in CAEO-mediated apoptosis of human liver carcinoma cells.

Essential oil from Siegesbeckia pubescens induces apoptosis through the mitochondrial pathway in human HepG2 cells.

Siegesbeckia pubescens (SP) has been used as a traditional medicine for the treatment of and inflammatory diseases. However, the activities of SP against hepatocellular carcinoma and the related mechanisms remain unclear. The present study aimed to examine the effects of the essential oil of SP (SPEO) on the proliferation of hepatocellular carcinoma cells and the possible mechanisms. The growth inhibition of HepG2 cells was analyzed by MTT assay. Hoechst 33258 and fluorescence microscopy were utilized to observe the nuclear morphological changes of apoptotic cells. Flow cytometry was used to detect cell apoptosis and cell cycle. The expressions of the target proteins were detected by Western blotting. The results showed that SPEO obviously inhibited the proliferation of HepG2 cells in a dose-dependent manner. SPEO activated a series of apoptotic proteins in HepG2 cells, increasing expression levels of Bax, caspase-3 and caspase-9, and decreasing the bcl-2 expression level. SPEO displayed promising anti-hepatocellular carcinoma activities in vitro, partly by inducing apoptosis in HepG2 cells through activating the mitochondrial pathway.

Caudatin targets TNFAIP1/NF-κB and cytochrome c/caspase signaling to suppress tumor progression in human uterine cancer.

Caudatin, a C-21 steroidal glyco-side isolated from Chinese herbs, has a long history of use for the treatment of multiple diseases, including cancers. However, the precise mechanisms of actions of caudatin in human uterine cancer cells remain unclear. In this study, we investigated the molecular mechanisms by which caudatin inhibits cell growth in human cervical carcinoma cell line (HeLa) and endometrial carcinoma cell line (HEC-1A). Treatment with caudatin promoted cell morphology change, inhibited cell proliferation, colony formation, migration and spheroid formation, and induced cell apoptosis. Our results showed that the expression of tumor necrosis factor; α-induced protein 1 (TNFAIP1) was downregulated in uterine cancer cells and tissues compared to paired adjacent non-tumor uterine tissues. Further molecular mechanism study showed that caudatin can directly regulate TNFAIP1 expression in a concentration-dependent manner and also associated with the downregulation of NF-κB and upregulation of BAX/BcL-2 ratio and caspase-3. Moreover, we found that overexpression of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in uterine cancer cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer. We found that caudatin inhibited tumorigenicity and upregulated TNFAIP1 in vivo. Taken together, caudatin impacts on cell proliferation, migration and apoptosis of uterine cancer cells by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of TNFAIP1/NF-κB signaling. Our findings provide new insights into understanding the anticancer mechanisms of caudatin in human uterine cancer therapy.

HPLC-based activity profiling of anti-hepatocellular carcinoma constituents from the Tibetan medicine, Caragana tibetica.

During the screening of a traditional Chinese folk herb library against HepG2 and Hep3B cell lines, the EtOAc extract from the Tibetan medicine, Caragana tibetica (CT-EtOAc) exhibited potential anti-hepatocellular carcinoma (anti-HCC) activity. HPLC-based activity profiling was performed for targeted identification of anti-HCC activity from CT-EtOAc by MS-directed purification method. CT-EtOAc was separated by time-based fractionation for further anti-HCC bioassay by a semipreparative HPLC column (150 mm × 10 mm i.d., 5 µm) with a single injection of 5 mg. Bioassay-guided and ESIMS-directed large scale purification was performed with a single injection of 400 mg of CT-EtOAc by peak-based fractionation. A 1.4-mm heavy wall micro NMR tube with z-gradient was used to measure one and two dimensional NMR spectra for the minor or trace amounts of components of the extract. Two active compounds could be elucidated as naringenin chalcone (CT-1) and 3-hydroxy-8, 9-dimethoxypterocarpan (CT-2) relevant to anti-HCC effects for the EtOAc extract of C. tibetica rapidly and unambiguously by this protocol.

Triterpene saponins from the stems of Entada phaseoloides.

Ten new triterpene saponins (1-10) have been isolated from the stems of Entada phaseoloides. Their structures were elucidated by spectroscopic analysis and chemical methods. Among these compounds, the aglycons of 6-10 are being reported for the first time, in this study, including 3ß,15α,16α-trihydroxy-11α,12α-epoxy olean-28,13ß-olide (6), 3ß,15α,16α-trihydroxy-11-oxo-olean-12-en-28-oic acids (7 and 8), and 3ß,15α,16α-trihydroxy-oleana-11,13(18)-dien-28-oic acids (9 and 10). The cytotoxic activities of all of these compounds were evaluated against HepG-2, A549, and Ec-1 cell lines.

Cytotoxic constituents from Psoralea corylifolia.

Bioassay directed isolation of the EtOAc extract from a traditional Chinese medicine Psoralea corylifolia resulted in the purification of two isoflavonoids, corylifols D (1) and E (2), along with four known ones. The structures of 1 and 2 were determined by extensive 1D and 2D NMR and MS data analyses. When tested against HepG2 and Hep3B hepatocellular carcinoma cell lines, corylifol A (4) displayed IC50 values of 4.6 and 13.5 µg/ml, respectively.